Target (protein/gene name): 1-deoxy-D-xylulose 5-phosphate reductoisomerase

NCBI Gene # or RefSeq#:
3191554
Protein ID (NP or XP #) or Wolbachia#: YP_170496.1
https://www.ncbi.nlm.nih.gov/protein/YP_170496.1

Organism: Francisella tularensis subsp. tularensis SCHU S4
    • amino acid sequences for different strains of the organism came out 100% identical
    • just use SCHU S4

Etiologic Risk Group (see link below): Risk Group 3

Background/Disease Information:
-also known as the "rabbit fever"
-bacterium found in animals (especially rodents, rabbits & hares)
-spread by: getting infected insect bites, handling infected sick or dead animal, eating/drinking contaminated food/water, or inhaling airborne bacteria
-not known to spread from person to person
-can be treated with antibiotics
-symptoms: sudden fever, chills, headaches, diarrhea, muscle aches, progressive weakness
-about 400 cases in the United States every year
-10-50 organisms can cause the disease/ highly infectious
http://www.bt.cdc.gov/agent/tularemia/facts.asp

Essentiality of this protein:
http://www.ncbi.nlm.nih.gov/pubmed?term=(1-deoxy-D-xylulose%205-phosphate%20reductoisomerase)%20AND%20Francisella%20Tularensis

Complex of enzymes:
EC#: 1.1.1.267

Link to BRENDA EC# page:
http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.267&Suchword=&organism%5B%5D=Francisella+tularensis&show_tm=0

Enzyme Assay information (spectrophotometric, coupled assay ?, reagents):
  • MEP synthase activity was evaluated at 22°C by spectrophotometrically monitoring the enzyme catalyzed oxidation of NADPH using an assay derived from that described by Takahashi et al.(http://www.ncbi.nlm.nih.gov/pubmed/9707569, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC21430/?tool=pubmed)
  • Assay mixtures (200 µL): contained 100 mM Tris pH 7.8, 25 mM MgCl2, 0.15 mM NADPH, 7 µM MEP synthase, and a variable concentration of DXP (Echelon Biosciences, Salt Lake City, UT)
  • Reagents: To determine cation specificity, assays were performed with 25 mM MgCl2, CaCl2, CoCl2, CuCl2, MnCl2, ZnCl2, or NiCl2
-- link to Sigma (or other company) page for assay or assay reagents (substrates)
  • 1-Deoxy-D-xylulose-5-phosphate sodium salt(13368 SIGMA): 1MG - $66.30 / 5MG-$264.50
(http://www.sigmaaldrich.com/catalog/product/sigma/13368?lang=en&region=US)


-- link to paper that contains assay information
from article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788227/?tool=pubmed
Structure Available (PDB or Homology model)
Screen Shot 2012-06-04 at 1.41.18 PM.png






















-- PDB # or closest PDB entry if homology model:
3IIE_A
http://www.pdb.org/pdb/explore/explore.do?structureId=3IIE

-- Query Coverage (if not direct match): 98%

-- Max Ident (if not direct match): 50%


Druggable Target (see Databases for this):

Current Inhibitors: fosmidomycin
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788227/?tool=pubmed

Expression Information (has it been expressed in bacterial cells):
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788227/?tool=pubmed

http://pubs.acs.org/doi/full/10.1021/bi047312p for E.coli
Purification Method:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788227/?tool=pubmed

http://pubs.acs.org/doi/full/10.1021/bi047312p for E.coli

Image of protein (PyMol or etc):
3iie_bio_r_500.jpg
1-deoxy-D-xylulose 5-phosphate reductoisomerase from Yersinia pestis (3IIE)


Amino Acid Sequence:
>fid|1288049|locus|FTT1574c| 1-deoxy-D-xylulose 5-phosphate reductoisomerase [Francisella tularensis subsp. tularensis SCHU S4]
MFKKTKITILGATGSIGDSTLAVIRETNDFEVFALTAFSNVEKLAELCQEFKPKFAVVPD LSKKQKLQSLVTDVEVLVGESGLEKVSSLAEIDIVMSAIVGIAGLKPTFAAAKAGKKILL ANKESLVTAGHLLIDEVVKNNAQLIPVDSEHNAIFQCIDNHDKKCLPEIDKIILTASGGP FRDKQLHELTDVTPEQACNHPNWQMGRKISVDSSTMVNKALEVIEAYWLFSVSADKIGVL IHPQSVTHSMVRYVDGSYIAQLGVPDMKTPIANAMYYPKRGSVNVESLDFTKYQLTFREA CFERFEALKIVFNNLQNKNYAANIVFNAANEELVAAFLNKKIKYLEIIEVNKKVTKELNF ENPKNIEEVFEIDRKTREYVDSVLG
length of your protein in Amino Acids 385

Molecular Weight of your protein in kiloDaltons using the Expasy ProtParamwebsite: 42847.4kDa

Molar Extinction coefficient of your protein at 280 nm wavelength:
Ext. coefficient 24660 <Abs 0.1% (=1 g/l) 0.576, assuming all pairs of Cys residues form cystines>
Ext. coefficient 24410 <Abs 0.1% (=1 g/l) 0.570, assuming all Cys residues are reduced)>

CDS Gene Sequence:
<span style="background-color: #ffffff; text-align: left; vertical-align: baseline;">>gi|255961454:c1637259-1636102 Francisella tularensis subsp. tularensis SCHU S4 chromosome, complete genome
<span class="ff_line" style="vertical-align: baseline;">ATGTTTAAAAAAACTAAGATTACTATATTAGGAGCTACAGGATCTATAGGTGATAGCACTTTAGCTGTTA
TTAGAGAGACTAATGATTTTGAAGTTTTTGCATTAACTGCATTTAGTAATGTTGAAAAGCTGGCAGAGCT
ATGTCAAGAGTTTAAGCCTAAATTTGCTGTAGTTCCAGACTTGTCAAAAAAACAAAAGTTACAATCATTA
GTTACTGATGTTGAGGTTTTGGTTGGTGAAAGTGGGCTTGAAAAAGTATCTAGCTTAGCTGAAATTGATA
TTGTCATGTCTGCTATAGTTGGTATAGCAGGGTTAAAACCAACCTTTGCAGCAGCTAAAGCTGGTAAGAA
AATTTTGCTTGCTAATAAAGAATCTTTGGTAACAGCAGGACACTTGCTGATAGATGAGGTTGTAAAGAAT
AATGCTCAACTTATTCCTGTGGATAGTGAACATAATGCTATATTTCAGTGTATTGATAATCATGATAAGA
AGTGTTTGCCAGAGATTGATAAGATAATTTTAACAGCATCTGGAGGTCCTTTTAGAGACAAACAACTACA
TGAGTTAACGGATGTAACACCCGAGCAAGCATGCAATCATCCTAATTGGCAAATGGGCAGAAAAATATCG
GTTGATTCATCAACTATGGTAAATAAAGCGTTAGAAGTTATCGAAGCGTATTGGCTTTTTTCTGTTTCAG
CTGATAAAATAGGCGTTCTGATTCATCCGCAGAGTGTAACTCATTCTATGGTCAGATATGTTGATGGTAG
CTATATAGCGCAGTTAGGTGTGCCTGATATGAAAACACCTATAGCCAACGCAATGTACTATCCAAAGAGA
GGATCAGTTAACGTTGAGAGCTTAGATTTTACAAAATATCAGCTAACCTTCAGAGAAGCTTGTTTTGAAA
GATTTGAAGCTTTGAAAATAGTTTTTAATAATTTACAAAATAAAAATTATGCTGCTAACATAGTTTTTAA
TGCTGCTAATGAGGAGCTTGTGGCTGCATTTTTAAACAAAAAAATTAAATATTTAGAGATAATAGAAGTA
AACAAAAAAGTAACAAAAGAGTTAAATTTTGAGAATCCAAAAAATATAGAAGAAGTTTTTGAAATAGATA
GAAAAACTCGTGAATATGTGGATTCTGTTTTGGGGTAA</span></span>
GC% Content for gene: 8.94%

CDS Gene Sequence (codon optimized) - after having done Primer Design:
1 ATGTTCAAAAAAACCAAAATCACCATCCTGGGTGCGACCGGTTCTATCGGTGACTCTACC
  61 CTGGCGGTTATCCGTGAAACCAATGATTTCGAAGTTTTCGCGCTGACCGCGTTCTCTAAC
 121 GTTGAGAAACTGGCGGAACTGTGCCAGGAATTCAAACCGAAATTTGCGGTTGTTCCTGAT
 181 CTGTCTAAAAAACAGAAACTCCAGTCTCTCGTTACCGACGTTGAAGTGCTGGTTGGTGAA
 241 TCTGGTCTGGAAAAAGTTTCTTCTCTGGCTGAGATCGACATTGTTATGTCTGCGATCGTT
 301 GGTATCGCGGGTCTGAAACCGACCTTTGCGGCAGCGAAAGCGGGTAAGAAAATCCTGCTG
 361 GCGAACAAAGAGTCTCTGGTTACCGCCGGTCATCTGCTGATCGACGAAGTTGTTAAGAAC
 421 AACGCCCAACTGATCCCGGTGGATTCTGAACACAACGCGATCTTCCAGTGCATTGACAAC
 481 CACGACAAAAAATGCCTGCCGGAAATCGATAAAATCATCCTGACTGCGTCTGGTGGTCCG
 541 TTCCGTGACAAACAGCTGCACGAACTGACGGACGTTACCCCAGAGCAGGCGTGTAATCAC
 601 CCGAACTGGCAGATGGGTCGTAAAATCTCTGTCGACTCTTCTACGATGGTAAACAAAGCC
 661 CTGGAAGTTATCGAAGCTTACTGGCTGTTCTCTGTTTCTGCGGACAAAATCGGTGTTCTG
 721 ATCCACCCGCAGTCTGTTACCCACTCTATGGTTCGTTACGTAGACGGCTCTTATATTGCT
 781 CAACTCGGTGTCCCTGACATGAAAACCCCGATTGCGAACGCCATGTACTATCCTAAACGT
 841 GGTTCTGTTAATGTTGAATCCCTGGACTTCACGAAGTACCAGCTGACCTTCCGCGAAGCG
 901 TGCTTCGAACGTTTTGAAGCTCTGAAAATTGTTTTCAACAACCTGCAGAACAAAAACTAC
 961 GCGGCCAACATCGTATTCAACGCCGCGAACGAAGAACTGGTTGCGGCCTTCCTGAACAAG
1021 AAGATCAAATACCTGGAGATCATTGAAGTAAATAAGAAGGTTACCAAAGAGCTGAATTTC
1081 GAGAACCCTAAAAACATTGAGGAAGTCTTCGAGATTGACCGTAAAACGCGTGAGTATGTG
1141 GACTCTGTTCTGGGCTAA
GC% Content for gene (codon optimized): 48.22%

Primer design results for pNIC-Bsa4 cloning (list seqeunces of all of your ~40 nt long primers):
ATGTTCAAAAAAACCAAAATCACCATCC

CCAGGGTAGAGTCACCGATAGAACCGGTCGCACCCAGGATGGTGATTTTGGTTTTTTTGA

TATCGGTGACTCTACCCTGGCGGTTATCCGTGAAACCAATGATTTCGAAGTTTTCGCGCT

GCACAGTTCCGCCAGTTTCTCAACGTTAGAGAACGCGGTCAGCGCGAAAACTTCGAAATC

AACTGGCGGAACTGTGCCAGGAATTCAAACCGAAATTTGCGGTTGTTCCTGATCTGTCTA

CTTCAACGTCGGTAACGAGAGACTGGAGTTTCTGTTTTTTAGACAGATCAGGAACAACCG

CTCTCGTTACCGACGTTGAAGTGCTGGTTGGTGAATCTGGTCTGGAAAAAGTTTCTTCTC

CCAACGATCGCAGACATAACAATGTCGATCTCAGCCAGAGAAGAAACTTTTTCCAGACCA

GTTATGTCTGCGATCGTTGGTATCGCGGGTCTGAAACCGACCTTTGCGGCAGCGAAAGCG

GGCGGTAACCAGAGACTCTTTGTTCGCCAGCAGGATTTTCTTACCCGCTTTCGCTGCCGC

AGAGTCTCTGGTTACCGCCGGTCATCTGCTGATCGACGAAGTTGTTAAGAACAACGCCCA

TGGAAGATCGCGTTGTGTTCAGAATCCACCGGGATCAGTTGGGCGTTGTTCTTAACAACT

AACACAACGCGATCTTCCAGTGCATTGACAACCACGACAAAAAATGCCTGCCGGAAATCG

TTGTCACGGAACGGACCACCAGACGCAGTCAGGATGATTTTATCGATTTCCGGCAGGCAT

TGGTCCGTTCCGTGACAAACAGCTGCACGAACTGACGGACGTTACCCCAGAGCAGGCGTG

AGTCGACAGAGATTTTACGACCCATCTGCCAGTTCGGGTGATTACACGCCTGCTCTGGGG

GGTCGTAAAATCTCTGTCGACTCTTCTACGATGGTAAACAAAGCCCTGGAAGTTATCGAA

ACCGATTTTGTCCGCAGAAACAGAGAACAGCCAGTAAGCTTCGATAACTTCCAGGGCTTT

TTCTGCGGACAAAATCGGTGTTCTGATCCACCCGCAGTCTGTTACCCACTCTATGGTTCG

GGGACACCGAGTTGAGCAATATAAGAGCCGTCTACGTAACGAACCATAGAGTGGGTAACA

TGCTCAACTCGGTGTCCCTGACATGAAAACCCCGATTGCGAACGCCATGTACTATCCTAA

TCGTGAAGTCCAGGGATTCAACATTAACAGAACCACGTTTAGGATAGTACATGGCGTTCG

TGAATCCCTGGACTTCACGAAGTACCAGCTGACCTTCCGCGAAGCGTGCTTCGAACGTTT

TTTTTGTTCTGCAGGTTGTTGAAAACAATTTTCAGAGCTTCAAAACGTTCGAAGCACGCT

TCAACAACCTGCAGAACAAAAACTACGCGGCCAACATCGTATTCAACGCCGCGAACGAAG

TCCAGGTATTTGATCTTCTTGTTCAGGAAGGCCGCAACCAGTTCTTCGTTCGCGGCGTTG

GAACAAGAAGATCAAATACCTGGAGATCATTGAAGTAAATAAGAAGGTTACCAAAGAGCT

AGACTTCCTCAATGTTTTTAGGGTTCTCGAAATTCAGCTCTTTGGTAACCTTCTTATTTA

CCCTAAAAACATTGAGGAAGTCTTCGAGATTGACCGTAAAACGCGTGAGTATGTGGACTC

TTAGCCCAGAACAGAGTCCACATACTCACGCG

Primer design results for 'tail' primers (this is just 2 sequences):


Link to Final Results Logfile
http://helixweb.nih.gov/tmp/dnaworks_1338926014p1697_2055/LOGFILE.txt

Upstream
TACTTCCAATCCATGTTCAAAAAAACCAAAATC
Downstream
TATCCACCTTTACTGTTAGCCCAGAACAGAGTC


>filtered DNA sequence consisting of 1158 bases

>filtered DNA sequence consisting of 1158 bases. ATGTTCAAAAAAACCAAAATCACCATCCTGGGTGCGACCGGTTCTATCGGTGACTCTACC CTGGCGGTTATCCGTGAAACCAATGATTTCGAAGTTTTCGCGCTGACCGCGTTCTCTAAC GTTGAGAAACTGGCGGAACTGTGCCAGGAATTCAAACCGAAATTTGCGGTTGTTCCTGAT CTGTCTAAAAAACAGAAACTCCAGTCTCTCGTTACCGACGTTGAAGTGCTGGTTGGTGAA TCTGGTCTGGAAAAAGTTTCTTCTCTGGCTGAGATCGACATTGTTATGTCTGCGATCGTT GGTATCGCGGGTCTGAAACCGACCTTTGCGGCAGCGAAAGCGGGTAAGAAAATCCTGCTG GCGAACAAAGAGTCTCTGGTTACCGCCGGTCATCTGCTGATCGACGAAGTTGTTAAGAAC AACGCCCAACTGATCCCGGTGGATTCTGAACACAACGCGATCTTCCAGTGCATTGACAAC CACGACAAAAAATGCCTGCCGGAAATCGATAAAATCATCCTGACTGCGTCTGGTGGTCCG TTCCGTGACAAACAGCTGCACGAACTGACGGACGTTACCCCAGAGCAGGCGTGTAATCAC CCGAACTGGCAGATGGGTCGTAAAATCTCTGTCGACTCTTCTACGATGGTAAACAAAGCC CTGGAAGTTATCGAAGCTTACTGGCTGTTCTCTGTTTCTGCGGACAAAATCGGTGTTCTG ATCCACCCGCAGTCTGTTACCCACTCTATGGTTCGTTACGTAGACGGCTCTTATATTGCT CAACTCGGTGTCCCTGACATGAAAACCCCGATTGCGAACGCCATGTACTATCCTAAACGT GGTTCTGTTAATGTTGAATCCCTGGACTTCACGAAGTACCAGCTGACCTTCCGCGAAGCG TGCTTCGAACGTTTTGAAGCTCTGAAAATTGTTTTCAACAACCTGCAGAACAAAAACTAC GCGGCCAACATCGTATTCAACGCCGCGAACGAAGAACTGGTTGCGGCCTTCCTGAACAAG AAGATCAAATACCTGGAGATCATTGAAGTAAATAAGAAGGTTACCAAAGAGCTGAATTTC GAGAACCCTAAAAACATTGAGGAAGTCTTCGAGATTGACCGTAAAACGCGTGAGTATGTG
GACTCTGTTCTGGGCTAA


Upstream

33bp

GC Content: 30.3%

Mg++ Concentration (mM)
Melting Temperature (°C)
0
57.6
1.5
65.8
2
66.4
4
67.3
6
68.2

Downstream

33bp

GC Content: 45.5%

Mg++ Concentration (mM)
Melting Temperature (°C)
0
62.1
1.5
69.3
2
69.8
4
70.7
6
71.2
Primers named as "FrTu_DXR_FOR & FrTu_DXR_REV"